scholarly journals Dasatinib increases endothelial permeability leading to pleural effusion

2018 ◽  
Vol 51 (1) ◽  
pp. 1701096 ◽  
Author(s):  
Carole Phan ◽  
Etienne-Marie Jutant ◽  
Ly Tu ◽  
Raphaël Thuillet ◽  
Andrei Seferian ◽  
...  
Keyword(s):  
Pleural Effusion ◽  
Kinase Inhibitor ◽  
Umbilical Vein ◽  
Endothelial Permeability ◽  
Cell Junctions ◽  
Dependent Manner ◽  
Vascular Endothelial ◽  
Umbilical Vein Endothelial Cells

Pleural effusion is a frequent side-effect of dasatinib, a second-generation tyrosine kinase inhibitor used in the treatment of chronic myelogenous leukaemia. However, the underlying mechanisms remain unknown. We hypothesised that dasatinib alters endothelial integrity, resulting in increased pulmonary vascular endothelial permeability and pleural effusion.To test this, we established the first animal model of dasatinib-related pleural effusion, by treating rats with a daily regimen of high doses of dasatinib (10 mg·kg−1·day−1 for 8 weeks).Pleural ultrasonography revealed that rats chronically treated with dasatinib developed pleural effusion after 5 weeks. Consistent with these in vivo observations, dasatinib led to a rapid and reversible increase in paracellular permeability of human pulmonary endothelial cell monolayers as reflected by increased macromolecule passage, loss of vascular endothelial cadherin and zonula occludens-1 from cell–cell junctions, and the development of actin stress fibres. These results were replicated using human umbilical vein endothelial cells and confirmed by decreased endothelial resistance. Interestingly, we demonstrated that this increased endothelial permeability is a reactive oxygen species (ROS)-dependent mechanism in vitro and in vivo using a cotreatment with an antioxidant agent, N-acetylcysteine.This study shows that dasatinib alters pulmonary endothelial permeability in a ROS-dependent manner in vitro and in vivo leading to pleural effusion.

scholarly journals A Protective Role of Paeoniflorin in Fluctuant Hyperglycemia-Induced Vascular Endothelial Injuries through Antioxidative and Anti-Inflammatory Effects and Reduction of PKCβ1

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Jing-Shang Wang ◽  
Ye Huang ◽  
Shuping Zhang ◽  
Hui-Jun Yin ◽  
Lei Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Protein Level ◽  
Umbilical Vein ◽  
Protective Role ◽  
Vascular Endothelial ◽  
Glucose Levels ◽  
Umbilical Vein Endothelial Cells

Hyperglycemia fluctuation is associated with diabetes mellitus (DM) complications when compared to persistent hyperglycemia. Previous studies have shown that paeoniflorin (PF), through its antiapoptosis, anti-inflammation, and antithrombotic properties, effectively protects against cardiovascular and cerebrovascular disease. However, the mechanism underlying the protection from PF against vascular injuries induced by hyperglycemia fluctuations remains poorly understood. Herein, we investigated the potential protective role of PF on human umbilical vein endothelial cells (HUVECs) subjected to intermittent glucose levels in vitro and in DM rats with fluctuating hyperglycemia in vivo. A remarkable increased apoptosis associated with elevated inflammation, increased oxidative stress, and high protein level of PKCβ1 was induced in HUVECs by intermittently changing glucose for 8 days, and PF recovered those detrimental changes. LY333531, a potent PKCβ1 inhibitor, and metformin manifested similar effects. Additionally, in DM rats with fluctuating hyperglycemia, PF protected against vascular damage as what has been observed in vitro. Taken together, PF attenuates the vascular injury induced by fluctuant hyperglycemia through oxidative stress inhibition, inflammatory reaction reduction, and PKCβ1 protein level repression, suggesting its perspective clinical usage.

scholarly journals Aspergillus fumigatus inhibits angiogenesis through the production of gliotoxin and other secondary metabolites

Blood ◽  
2009 ◽  
Vol 114 (26) ◽  
pp. 5393-5399 ◽  
Author(s):  
Ronen Ben-Ami ◽  
Russell E. Lewis ◽  
Konstantinos Leventakos ◽  
Dimitrios P. Kontoyiannis
Keyword(s):  
Invasive Aspergillosis ◽  
Aspergillus Fumigatus ◽  
Capillary Tube ◽  
Umbilical Vein ◽  
Tube Formation ◽  
Dependent Manner ◽  
Antiangiogenic Effect ◽  
Umbilical Vein Endothelial Cells

AbstractIn susceptible hosts, angioinvasion by Aspergillus fumigatus triggers thrombosis, hypoxia, and proinflammatory cytokine release, all of which are stimuli for angiogenesis. We sought to determine whether A fumigatus directly modulates angiogenesis. A fumigatus culture filtrates profoundly inhibited the differentiation, migration, and capillary tube formation of human umbilical vein endothelial cells in vitro. To measure angiogenesis at the site of infection, we devised an in vivo Matrigel assay in cyclophosphamide-treated BALB/c mice with cutaneous invasive aspergillosis. Angiogenesis was significantly suppressed in Matrigel plugs implanted in A fumigatus–infected mice compared with plugs from uninfected control mice. The antiangiogenic effect of A fumigatus was completely abolished by deletion of the global regulator of secondary metabolism, laeA, and to a lesser extent by deletion of gliP, which controls gliotoxin production. Moreover, pure gliotoxin potently inhibited angiogenesis in vitro in a dose-dependent manner. Finally, overexpression of multiple angiogenesis mediator–encoding genes was observed in the lungs of cortisone-treated mice during early invasive aspergillosis, whereas gene expression returned rapidly to baseline levels in cyclophosphamide/cortisone-treated mice. Taken together, these results indicate that suppression of angiogenesis by A fumigatus both in vitro and in a neutropenic mouse model is mediated through secondary metabolite production.

scholarly journals Role of Glial Cell Line-Derived Neurotrophic Factor in Adipose Tissue Extract-Induced Angiogenesis in Mice

2021 ◽  
Author(s):  
Renpeng Zhou ◽  
Chuang Yin ◽  
Weiwei Bian ◽  
Chen Wang
Keyword(s):  
Skin Graft ◽  
Umbilical Vein ◽  
Skin Condition ◽  
Tube Formation ◽  
Vascular Density ◽  
Dependent Manner ◽  
Dermal Thickness ◽  
Umbilical Vein Endothelial Cells

Abstract Our present study is aimed to evaluate the effects of adipose-derived extracts (AT-Ex) and GDNF within the extracts on skin graft. AT-Ex was harvest from fresh human lipoaspirates with centrifugation, emulsification and lysing by cycles of freeze and thawing. Concentrations of GDNF, VEGF and bFGF were detected by ELISA. AT-Ex and anti-GDNF-antibody-coupled AT-Ex were further used to test their ability to promote tube formation using human umbilical vein endothelial cells (HUVECs) and stimulate angiogenesis in nude skin-graft models. The results demonstrated that abundant GDNF, VEGF and bFGF were detected in AT-Ex, with GDNF displaying the highest concentration. AT-Ex significantly promoted the tube formation ability of HUVECs in vitro, with a dosage-dependent manner, while this ability was partially impaired when the anti-GDNF antibody was conjugated. In vivo, The AT-Ex treatment increased dermal thickness, augmented dermal proliferation and increased vascular density and GDNF contributed greatly to the AT-Ex effect in improvement the grafted skin condition by promoting angiogenesis in vivo. Our results suggested that critical effect of GDNF from AT-Ex on improvement skin graft condition.

scholarly journals Bivalirudin Attenuates Thrombin-Induced Endothelial Hyperpermeability via S1P/S1PR2 Category: Original Articles

2021 ◽  
Vol 12 ◽  
Author(s):  
Haowen Ye ◽  
Yizhi Zhang ◽  
Yihui Huang ◽  
Biao Li ◽  
Ruhao Cao ◽  
...  
Keyword(s):  
Protective Effect ◽  
Umbilical Vein ◽  
Endothelial Permeability ◽  
Control Group ◽  
Sphingosine 1 Phosphate ◽  
Organ Tissue ◽  
Probe Assay ◽  
Umbilical Vein Endothelial Cells

Aims: To explore the role of the Sphingosine 1-Phosphate (S1P)/Receptor2 (S1PR2) pathway in thrombin-induced hyperpermeability (TIP) and to test whether bivalirudin can reverse TIP via the S1P-S1PRs pathway.Methods and Results: Using western blot, we demonstrated that Human umbilical vein endothelial cells (HUVECs) that were cultured with 2 U/ml thrombin showed significantly increased S1PR2 expression while S1PR1and three kept unchanged. Such increment was attenuated by JTE-013 pretreatment and by presence of bivalirudin. Exposure of 2 U/ml of thrombin brought a higher level of S1P both intracellularly and extracellularly within the HUVECs by using ELISA detecting. Thrombin induced S1P and S1PR2 increment was restored by usage of PF543 and bivalirudin. Bivalirudin alone did not influenced the level of S1P and S1PR1,2, and S1PR3 compare to control group. As a surrogate of cytoskeleton morphology, phalloidin staining and immunofluorescence imaging were used. Blurry cell edges and intercellular vacuoles or spaces were observed along thrombin-exposed HUVECs. Presence of JTE-013 and bivalirudin attenuated such thrombin-induced permeability morphological change and presence of heparin failed to show the protective effect. Transwell chamber assay and probe assay were used to measure and compare endothelial permeability in vitro. An increased TIP was observed in HUVECs cultured with thrombin, and coculture with bivalirudin, but not heparin, alleviated this increase. JTE-013 treatment yielded to similar TIP alleviating effect. In vivo, an Evans blue assay was used to test subcutaneous and organ microvascular permeability after the treatment of saline only, thrombin + saline, thrombin + bivalirudin, thrombin + heparin or thrombin + JTE-013. Increased subcutaneous and organ tissue permeability after thrombin treatment was observed in thrombin + saline and thrombin + heparin groups while treatment of bivalirudin and JTE-013 absent this effect.Conclusion: S1P/S1PR2 mediates TIP by impairing vascular endothelial barrier function. Unlike heparin, bivalirudin effectively blocked TIP by inhibiting the thrombin-induced S1P increment and S1PR2 expression, suggesting the novel endothelial protective effect of bivalirudin under pathological procoagulant circumstance.

scholarly journals Deacylated lipopolysaccharide inhibits neutrophil adherence to endothelium induced by lipopolysaccharide in vitro.

1987 ◽  
Vol 165 (5) ◽  
pp. 1393-1402 ◽  
Author(s):  
T H Pohlman ◽  
R S Munford ◽  
J M Harlan
Keyword(s):  
Fatty Acids ◽  
Umbilical Vein ◽  
Surface Expression ◽  
Specific Cell ◽  
Dependent Manner ◽  
Toxic Activity ◽  
Neutrophil Adherence ◽  
Umbilical Vein Endothelial Cells

Selective deacylation of the nonhydroxylated fatty acids from S. typhimurium LPS by an acyloxyacyl hydrolase isolated from leukocytes reduces toxic activity of LPS in vivo. We examined the effect of deacylated LPS on neutrophil adherence to human umbilical vein endothelial cells (HUVE). Pretreatment of HUVE with LPS (13 ng/ml for 4 h) produced a marked increase in the adherence of subsequently added neutrophils. In contrast, there was no increase in the adherence of neutrophils to HUVE pretreated with deacylated LPS (up to 260 ng/ml for 4 h). Neutrophil adherence to HUVE pretreated with LPS decreased as the degree of LPS deacylation increased. Deacylated LPS was not only itself inactive, but it inhibited neutrophil-endothelial interactions induced by LPS. Neutrophil adherence to HUVE pretreated with LPS was inhibited by deacylated LPS in a dose-dependent manner. Complete inhibition of adherence was observed at a 20:1 ratio (wt/wt) of deacylated LPS to LPS. Significantly, inhibition of neutrophil adherence to HUVE pretreated with LPS was observed even when deacylated LPS was added to HUVE up to 60 min after LPS. Deacylated LPS, however, did not inhibit neutrophil adherence induced by pretreatment of HUVE with IL-1 or TNF-alpha. We conclude that enzymatic deacylation of the nonhydroxylated fatty acids of LPS abolishes the ability of LPS to induce surface expression of a neutrophil adherence promoting activity in HUVE. Furthermore, deacylated LPS inhibits neutrophil adherence to HUVE induced by LPS, perhaps by preventing the interaction of LPS with a specific cell-surface or intracellular target.

Ultrastructural observations on the in vitro cytoadherence of Plasmodium falciparum infected red blood cells

1990 ◽  
Vol 48 (3) ◽  
pp. 914-915
Author(s):  
D.J.P. Ferguson ◽  
A.R. Berendt ◽  
J. Tansey ◽  
K. Marsh ◽  
C.I. Newbold
Keyword(s):  
Plasmodium Falciparum ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Umbilical Vein ◽  
Cell Types ◽  
Amelanotic Melanoma ◽  
Cytoplasmic Process ◽  
Umbilical Vein Endothelial Cells

In human malaria, the most serious clinical manifestation is cerebral malaria (CM) due to infection with Plasmodium falciparum. The pathology of CM is thought to relate to the fact that red blood cells containing mature forms of the parasite (PRBC) cytoadhere or sequester to post capillary venules of various tissues including the brain. This in vivo phenomenon has been studied in vitro by examining the cytoadherence of PRBCs to various cell types and purified proteins. To date, three Ijiost receptor molecules have been identified; CD36, ICAM-1 and thrombospondin. The specific changes in the PRBC membrane which mediate cytoadherence are less well understood, but they include the sub-membranous deposition of electron-dense material resulting in surface deformations called knobs. Knobs were thought to be essential for cytoadherence, lput recent work has shown that certain knob-negative (K-) lines can cytoadhere. In the present study, we have used electron microscopy to re-examine the interactions between K+ PRBCs and both C32 amelanotic melanoma cells and human umbilical vein endothelial cells (HUVEC).We confirm previous data demonstrating that C32 cells possess numerous microvilli which adhere to the PRBC, mainly via the knobs (Fig. 1). In contrast, the HUVEC were relatively smooth and the PRBCs appeared partially flattened onto the cell surface (Fig. 2). Furthermore, many of the PRBCs exhibited an invagination of the limiting membrane in the attachment zone, often containing a cytoplasmic process from the endothelial cell (Fig. 2).

scholarly journals Generation of a Novel In Vitro Model to Study Endothelial Dysfunction from Atherothrombotic Specimens

2021 ◽  
Author(s):  
Susan Gallogly ◽  
Takeshi Fujisawa ◽  
John D. Hung ◽  
Mairi Brittan ◽  
Elizabeth M. Skinner ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Dysfunction ◽  
In Vitro Model ◽  
Umbilical Vein ◽  
Coronary Syndrome ◽  
Coronary Endothelial Cells ◽  
Vitro Model ◽  
Umbilical Vein Endothelial Cells

Abstract Purpose Endothelial dysfunction is central to the pathogenesis of acute coronary syndrome. The study of diseased endothelium is very challenging due to inherent difficulties in isolating endothelial cells from the coronary vascular bed. We sought to isolate and characterise coronary endothelial cells from patients undergoing thrombectomy for myocardial infarction to develop a patient-specific in vitro model of endothelial dysfunction. Methods In a prospective cohort study, 49 patients underwent percutaneous coronary intervention with thrombus aspiration. Specimens were cultured, and coronary endothelial outgrowth (CEO) cells were isolated. CEO cells, endothelial cells isolated from peripheral blood, explanted coronary arteries, and umbilical veins were phenotyped and assessed functionally in vitro and in vivo. Results CEO cells were obtained from 27/37 (73%) atherothrombotic specimens and gave rise to cells with cobblestone morphology expressing CD146 (94 ± 6%), CD31 (87 ± 14%), and von Willebrand factor (100 ± 1%). Proliferation of CEO cells was impaired compared to both coronary artery and umbilical vein endothelial cells (population doubling time, 2.5 ± 1.0 versus 1.6 ± 0.3 and 1.2 ± 0.3 days, respectively). Cell migration was also reduced compared to umbilical vein endothelial cells (29 ± 20% versus 85±19%). Importantly, unlike control endothelial cells, dysfunctional CEO cells did not incorporate into new vessels or promote angiogenesis in vivo. Conclusions CEO cells can be reliably isolated and cultured from thrombectomy specimens in patients with acute coronary syndrome. Compared to controls, patient-derived coronary endothelial cells had impaired capacity to proliferate, migrate, and contribute to angiogenesis. CEO cells could be used to identify novel therapeutic targets to enhance endothelial function and prevent acute coronary syndromes.

scholarly journals SiRNA Directed Against Annexin II Receptor Inhibits Angiogenesis via Suppressing MMP2 and MMP9 Expression

2015 ◽  
Vol 35 (3) ◽  
pp. 875-884 ◽  
Author(s):  
Hongyuan Song ◽  
Dongyan Pan ◽  
Weifeng Sun ◽  
Cao Gu ◽  
Yuelu Zhang ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Umbilical Vein ◽  
Tube Formation ◽  
Annexin Ii ◽  
Mmp9 Expression ◽  
Cell Arrest ◽  
Umbilical Vein Endothelial Cells

Background/Aims: Annexin II receptor (AXIIR) is able to mediate Annexin II signal and induce apoptosis, but its role in angiogenesis remains unclear. This study tries to investigate the role of AXIIR in angiogenesis and the plausible molecular mechanism. Methods/Results: RNA interference technology was used to silence AXIIR, and the subsequent effects in vitro and in vivo were evaluated thereafter. Our data indicated that human umbilical vein endothelial cells (HUVECs) expressed AXIIR and knockdown of AXIIR significantly inhibited HUVECs proliferation, adhesion, migration, and tube formation in vitro and suppressed angiogenesis in vivo. Furthermore, AXIIR siRNA induced cell arrest in the S/G2 phase while had no effect on cell apoptosis. We found that these subsequent effects might be via suppressing the expression of matrix metalloproteinase 2and matrix metalloproteinase 9. Conclusion: AXIIR participates in angiogenesis, and may be a potential therapeutic target for angiogenesis related diseases.

scholarly journals Citrus bergamiaRisso Elevates Intracellular Ca2+in Human Vascular Endothelial Cells due to Release of Ca2+from Primary Intracellular Stores

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Purum Kang ◽  
Seung Ho Han ◽  
Hea Kyung Moon ◽  
Jeong-Min Lee ◽  
Hyo-Keun Kim ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Channel Blocker ◽  
Vascular Endothelial Cells ◽  
Umbilical Vein ◽  
Dependent Manner ◽  
Vascular Endothelial ◽  
Concentration Dependent Manner ◽  
Carbonyl Cyanide ◽  
Intracellular Ca ◽  
Umbilical Vein Endothelial Cells

The purpose of the present study is to examine the effects of essential oil ofCitrus bergamiaRisso (bergamot, BEO) on intracellular Ca2+in human umbilical vein endothelial cells. Fura-2 fluorescence was used to examine changes in intracellular Ca2+concentration[Ca2+]i. In the presence of extracellular Ca2+, BEO increased[Ca2+]i, which was partially inhibited by a nonselective Ca2+channel blocker La3+. In Ca2+-free extracellular solutions, BEO increased[Ca2+]iin a concentration-dependent manner, suggesting that BEO mobilizes intracellular Ca2+. BEO-induced[Ca2+]iincrease was partially inhibited by a Ca2+-induced Ca2+release inhibitor dantrolene, a phospholipase C inhibitor U73122, and an inositol 1,4,5-triphosphate (IP3)-gated Ca2+channel blocker, 2-aminoethoxydiphenyl borane (2-APB). BEO also increased[Ca2+]iin the presence of carbonyl cyanide m-chlorophenylhydrazone, an inhibitor of mitochondrial Ca2+uptake. In addition, store-operated Ca2+entry (SOC) was potentiated by BEO. These results suggest that BEO mobilizes Ca2+from primary intracellular stores via Ca2+-induced and IP3-mediated Ca2+release and affect promotion of Ca2+influx, likely via an SOC mechanism.

scholarly journals Effect of aminaphtone on in vitro vascular permeability and capillary-like maintenance

2017 ◽  
Vol 33 (9) ◽  
pp. 592-599 ◽  
Author(s):  
Francesca Felice ◽  
Ester Belardinelli ◽  
Alessandro Frullini ◽  
Tatiana Santoni ◽  
Egidio Imbalzano ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Chronic Venous Insufficiency ◽  
Venous Insufficiency ◽  
Umbilical Vein ◽  
Three Dimensional ◽  
Endothelial Permeability ◽  
Human Umbilical Vein ◽  
Pre Treatment ◽  
Umbilical Vein Endothelial Cells

Objectives Aminaphtone, a naphtohydrochinone used in the treatment of capillary disorders, may affect oedema in chronic venous insufficiency. Aim of study is to investigate the effect of aminaphtone on vascular endothelial permeability in vitro and its effects on three-dimensional capillary-like structures formed by human umbilical vein endothelial cells. Method Human umbilical vein endothelial cells were treated with 50 ng/ml VEGF for 2 h and aminaphtone for 6 h. Permeability assay, VE-cadherin expression and Matrigel assay were performed. Results VEGF-induced permeability was significantly decreased by aminaphtone in a range concentration of 1–20 µg/ml. Aminaphtone restored VE-cadherin expression. Finally, 6 h pre-treatment with aminaphtone significantly preserved capillary-like structures formed by human umbilical vein endothelial cells on Matrigel up to 48 h compared to untreated cells. Conclusions Aminaphtone significantly protects endothelium permeability and stabilises endothelial cells organised in capillary-like structures, modulating VE-cadherin expression. These data might explain the clinical benefit of aminaphtone on chronic venous insufficiency.

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